Usefulness and limitations of E-cadherin and β-catenin in the classification of breast carcinomas in situ with mixed pattern

Abstract

BackgroundThe distinction between lobular neoplasia of the breast and ductal carcinoma in situ has important therapeutic implications. In some cases, it is very difficult to determine whether the morphology of the lesion is ductal or lobular. The aim of this study was to evaluate the value of E-cadherin and β-catenin expression through the immunophenotypical characterization of carcinoma in situ with mixed pattern (CISM).MethodsA total of 25 cases of CISM were analyzed considering cytology/mixed architecture (ductal and lobular), nuclear pleomorphism, loss of cell cohesion, and presence of comedonecrosis. The immunophenotype pattern was considered E-cadherin positive and β-catenin positive, or negative.ResultsNineteen (76%) cases presented a mixed cytology and / or architectural pattern, two (8%) presented nuclear pleomorphism, two (8%) presented mixed cytology and nuclear pleomorphism, and two (8%) presented comedonecrosis and nuclear pleomorphism. A complete positivity for E-cadherin and β-catenin was observed in 11 cases (44%). In one case, the lesion was negative for both markers and showed nuclear pleomorphis. Thirteen lesions showed negative staining in areas of lobular cytology and positive staining in cells presenting the ductal pattern.ConclusionsThe expression of E-cadherin and β-catenin, combined with cytological and architectural analysis, may highlight different immunophenotypes and improve classification of CISM.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1693384202970681

Metaplastic carcinoma of the breast: an immunohistochemical study

“…Demonstration of down regulation of this molecule is demonstrated by immunohistochemistry. Loss of E-cadherin is a very useful stain in the classification of breast carcinomas in situ with mixed pattern as well as it is useful in differentiating lobular from ductal carcinoma [ 14 ].…”

“…The differential of MBC include wide range of pathological diagnosis, including lobular carcinoma, Pleomorphic carcinoma and other rare sarcoma such as angiosarcoma. E-cadherin is a very useful stain in the classification of breast carcinomas with mixed pattern [ 14 ]. Also a rare entity that was recognized by the World Health Organization (WHO) classification of tumours of the breast adopts the terminology of Pleomorphic carcinoma(PC) should be included in the differential diagnosis.…”

Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium

“…Briefly, cells were either permeabilized with 0.5% peroxide and carbonyl-free Triton X-100 (Sigma-Aldrich) in cytoskeleton buffer (100 mM NaCl, 300 mM sucrose, 10 mM PIPES pH 6.8, 5 mM MgCl 2 , 1 mM pefabloc, 10 µg/ml aprotinin, 250 µM NaF) prior to fixation in 4% paraformaldehyde (Sigma-Aldrich), or directly fixed with 4% paraformaldehyde. Antibodies used were rabbit polyclonal against Cx43 (0.5 mg/ml; C6219, Sigma-Aldrich; Tong et al, 2009), Ki67 (100 μg/ml; VP-K451, Vector; Knezevic et al, 2015), mouse monoclonal against NuMA (1:2; B1C11, a gift from Dr Jeffrey Nickerson, University of Massachusetts, Worcester, MA; Vidi et al, 2011), ZO-1 (2.5 μg/ml; 33-9100, Life Technologies; Grand Island, NY; Mao et al, 2017), α-tubulin (1:500; T5168, Sigma-Aldrich; Piao et al, 2014), β-catenin (2.5 μg/ml; C19220, BD Biosciences; Gomes et al, 2013), E-cadherin (1:50; 610181, BD Biosciences; Elisha et al, 2018), and rat anti-α6 integrin (5 μg/ml; clone NKI-GoH3, EMD Millipore, Billerica, MA; Villa-Diaz et al, 2016). For immunostaining for lysosomal associated membrane 2 (LAMP-2) (1:100; mouse, A15464, Life Technologies), cells were fixed with methanol acetone solution (1:1 ratio) without permeabilization.…”

Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast

“…However, there were other conflicting diagnoses for these cases, including ADH (14%), DCIS (1.4%), and usual ductal hyperplasia (10%) [ 6 ]. In fact, the differential diagnosis of LN and intraductal proliferative lesions can be difficult, especially when concerning classic LN versus low-grade solid DCIS, and pleomorphic LCIS versus high-grade DCIS [ 2 , 18 ]. Despite the low number of pleomorphic LCIS cases in our study, the inter-observer agreement was poor (Kappa index = 0.22).…”